Diagnosing Fractionalization from the Spin Dynamics of Z2Z_2 Spin Liquids on the Kagome Lattice by Quantum Monte Carlo Simulations

Based on large-scale quantum Monte Carlo simulations, we examine the dynamical spin structure factor of the Balents-Fisher-Girvin kagome lattice quantum spin-$1/2$ model, which is known to harbor an extended $Z_2$ quantum spin liquid phase. We use a correlation-matrix sampling scheme combined with a stochastic analytic continuation method to resolve the spectral functions of this anisotropic quantum spin model with a three-site unit-cell. Based on this approach, we monitor the spin dynamics throughout the phase diagram of this model, from the XY-ferromagnetic region to the $Z_2$ quantum spin liquid regime. In the latter phase, we identify a gapped two-spinon continuum in the transverse scattering channel, which is faithfully modeled by an effective spinon tight-binding model. Within the longitudinal channel, we identify gapped vison excitations and exhibit indications for the translational symmetry fractionalization of the visons via an enhanced spectral periodicity.Comment: 6 pages, 9 figures, v2: published versio

Pulling the right viral levers: Engineering, screening and application of next-generation combinatorial AAV vectors

Adeno-associated viruses (AAVs) present powerful vectors for human gene therapy and biomedical research. They enable the delivery of transgenes to a broad range of target tissues. This allows persistent expression of reporter genes, therapeutic gene replacement and the delivery of control elements for manipulating endogenous gene expression. Transduction efficiency and specificity for on-target over off-target cells are critical factors driving vector safety and applicability. In this study, I engineered AAV capsids, promoters and knockdown tools with the goal of generating efficient and specific vector components for the next generation of cell-type-specific gene therapy vectors. In the first part of this doctoral work, I utilized Cas13d (CasRx) and short-hairpin (sh)RNA effectors to assess AAV-induced RNA degradation (knockdown). While CasRx showed promising knockdown of a Renilla luciferase reporter target, it failed to silence endogenous CD44, a potential driver of metabolic (non-alcoholic) steatohepatitis. shRNA effectors, however, allowed robust target knockdown of cellular RNAs (CD44 and ACE2) as well as SARS-CoV-2 viral RNA. Direct targeting of SARS-CoV-2 genomic RNA triggered the evolution of escape mutations within the viral target sites. This mutational escape was efficiently suppressed by multiplexing of three shRNAs in a single AAV vector, thereby allowing a sustained suppression of SARS-CoV-2 infection in Vero E6 cells. In the second part, I focused on improving screening conditions for promoters and AAV capsids. By assessing eYFP reporter expression in vivo for four promoter constructs individually, I could validate the findings of a previous promoter screen. This screen had utilized high-throughput barcode sequencing for parallel readout of a library of AAV-promoter constructs. I then applied this barcoding technique to dissect the activity of the GFAP promoter and truncated versions thereof. The GFAP promoter has previously mostly been used to induce astrocyte-specific transgene expression in the central nervous system. Strikingly, though, my results demonstrate a highly efficient GFAP promoter-driven transgene expression in human and murine hepatocytes. To optimize the directed evolution of AAV capsids, I modified conventional capsid library screening by altering selection parameters. This was achieved by (i) introducing a Cas9-based negative selection for the removal of unwanted variants from the capsid library, and (ii) by exploring and applying RNA-based functional selection. I could generate an RNA-based screening platform by driving the expression of cap from the ubiquitous CMV promoter instead of the endogenous p40. Both screening approaches proved applicable in cell culture settings. As RNA-driven selection offers a functional readout from both on- and off-target cells, I applied this approach for in vivo screening of an AAV6 peptide display library in mouse non-parenchymal liver cells. CMV promoter-driven cap expression enabled RNA-based readout of variant enrichment for on- and off-target cell-types. This demonstrated improved selectivity for RNA- over conventional DNA-based screening and facilitated the identification of functional, cell-type-specific capsid candidates. In conclusion, my results show the development of efficient combinatorial shRNA-based knockdown vectors for inhibiting CD44 expression or SARS-CoV-2 infection in vitro. Furthermore, I could implement improvements in capsid and promoter screening. This allowed the detection of highly functional variants with potential future applications in the development of novel gene therapy vectors

Does weak discernibility determine metaphysics?

Dos entidades son débilmente discernibles cuando entre ellas se mantiene una relación irreflexiva y simétrica. En la actualidad no se discute que la discernibilidad débil se da en la mecánica cuántica. Las consecuencias ontológicas de la discernibilidad débil, sin embargo, no están muy claras. Parte de la literatura al respecto parece implicar que la discernibilidad débil apunta, en la mecánica cuántica, a una metafísica determinada. En este artículo analizaremos la contribución metafísica de la discernibilidad débil a la mecánica cuántica y argumentaremos que, al contrario de lo que se sostiene en parte de la literatura actual, la discernibilidad débil no proporciona una determinación completamente.; Two entities are weakly discernible when an irreflexive and symmetric relation holds between them. That weak discernibility holds in quantum mechanics is fairly uncontroversial nowadays. The ontological consequences of weak discernibility, however, are far from clear. Part of the literature seems to imply that weak discernibility points to a definite metaphysics to quantum mechanics. In this paper we shall discuss the metaphysical contribution of weak discernibility to quantum mechanics and argue that, contrary to part of current literature, it does not provide for a fully naturalistic determination of metaphysics. Underdetermination of the metaphysics still plagues the way of the naturalist

Logički relativizam kroz logičke kontekste

We advance an approach to logical contexts that grounds the claim that logic is a local matter: distinct contexts require distinct logics. The approach results from a concern about context individuation, and holds that a logic may be constitutive of a context or domain of application. We add a naturalistic component: distinct domains are more than mere technical curiosities; as intuitionistic mathematics testifies, some of the distinct forms of inference in different domains are actively pursued as legitimate fields of research in current mathematics, so, unless one is willing to revise the current scientific practice, generalism must go. The approach is advanced by discussing some tenets of a similar argument advanced by Shapiro, in the context of logic as models approach. In order to make our view more appealing, we reformulate a version of logic as models approach following naturalistic lines, and bring logic closer to the use of models in science.Zastupamo pristup logičkim kontekstima koji utemeljuju tvrdnju da je logika lokalna stvar: različiti konteksti zahtijevaju različitu logiku. Pristup je se temelji na razmišljanju o individuaciji konteksta i smatra da logika može biti konstitutivna za kontekst ili domenu primjene. Dodajemo naturalističku komponentu: različite domene su više od samo tehničkih zanimljivosti; Kako intuitistička matematika svjedoči, neki od različitih oblika zaključivanja u različitim područjima aktivno se provode kao legitimna područja istraživanja u sadašnjoj matematici, pa, osim ako je netko spreman revidirati sadašnju znanstvenu praksu, generalizam se mora napustiti. Ovaj pristup se brani kroz raspravu nekih komponenti sličnog argumenta kojeg zastupa Shapiro, u kontekstu shvaćanja logike kao modela. Kako bi se naše gledište učinilo privlačnijim, slijedimo naturalističku verziju pristupa logici kao modelu i približavamo logiku kako se modeli koriste u znanostima

Finite-Temperature Dynamics and Thermal Intraband Magnon Scattering in Haldane Spin-One Chains

The antiferromagnetic spin-one chain is considerably one of the most fundamental quantum many-body systems, with symmetry protected topological order in the ground state. Here, we present results for its dynamical spin structure factor at finite temperatures, based on a combination of exact numerical diagonalization, matrix-product-state calculations and quantum Monte Carlo simulations. Open finite chains exhibit a sub-gap band in the thermal spectral functions, indicative of localized edge-states. Moreover, we observe the thermal activation of a distinct low-energy continuum contribution to the spin spectral function with an enhanced spectral weight at low momenta and its upper threshold. This emerging thermal spectral feature of the Haldane spin-one chain is shown to result from intra-band magnon scattering due to the thermal population of the single-magnon branch, which features a large bandwidth-to-gap ratio. These findings are discussed with respect to possible future studies on spin-one chain compounds based on inelastic neutron scattering.Comment: 10 pages with 11 figures total (including Supplemental Material); changes in v2: new Figs. S1 and S5, Fig. S3 expanded + related discussion + many smaller modifications to match published versio

Better than a lens -- Increasing the signal-to-noise ratio through pupil splitting

Lenses are designed to fulfill Fermats principle such that all light interferes constructively in its focus, guaranteeing its maximum concentration. It can be shown that imaging via an unmodified full pupil yields the maximum transfer strength for all spatial frequencies transferable by the system. Seemingly also the signal-to-noise ratio (SNR) is optimal. The achievable SNR at a given photon budget is critical especially if that budget is strictly limited as in the case of fluorescence microscopy. In this work we propose a general method which achieves a better SNR for high spatial frequency information of an optical imaging system, without the need to capture more photons. This is achieved by splitting the pupil of an incoherent imaging system such that two (or more) sub-images are simultaneously acquired and computationally recombined. We compare the theoretical performance of split pupil imaging to the non-split scenario and implement the splitting using a tilted elliptical mirror placed at the back-focal-plane (BFP) of a fluorescence widefield microscope